We plan to study in depth the pathogenesis of fever in experimental models of delayed hypersensitivity (DHS) and immediate hypersensitivity (IHS). In addition, the mechanism for fevers caused by non-specific mitogens such as concanavalin A and phytohemagglutinin will be investigated. The contributions of various tissues and cell types, both animal (rabbit and guinea pig) and human, will be examined. In states of DHS, we hope to define the role of the activated lymphocyte in producing a putative lymphokine that, in turn, stimulates phagocytic cells to produce endogenous pyrogen (EP) in vitro. In fever due to immune complexes, the nature of the necessary interactions between antigen, antibody, and cells or tissues will be examined. Pyrogen production by mononuclear phagocytes will be studied to determine the responses of these cells to stimuli associated with delayed and immediate hypersensitivity reactions. Such studies of in vivo and in vitro models of immune fever will elucidate the kinds of effective stimuli, the responding cells, and the pathways of pyrogen production.